The objectives of the proposed research are to determine whether a viral agent can be implicated in the etiology of Paget's disease of bone. Recent electron microscopic studies of bone cells in Paget's disease have revealed the presence of characteristic nuclear inclusions in the osteoclasts. These inclusions most closely resemble viral necleocapsids of the paramyxovirus type. These have also been found in the cells cultured from Paget's disease bone. The clinical course of the disease is consistent with a slow virus disease. Bone has been obtained from patients undergoing orthopedic surgery to correct disabilities of the disease. Specific immunofluorescent and immunoperoxidase methods have been used to search for a virus in bone and in cells derived from bone. Preliminary results have been positive to certain antibodies. These results are being confirmed and extended at the present time. In addition, rescue of a defective virus will be attempted by co-cultivation or fusion with permissive cell lines. The second year of the grant will be used to pass cells, tissue and extracts in animals in the attempt to isolate a virus or produce a pathologic process indicative of the presence of a virus.